Dr Gluz on the Rationale for the WSG-TP-II Trial in HR+/HER2+ Early Breast Cancer

Oleg Gluz, MD, chief physician, Breast Center Niederrhein; West German Study Group, discusses the rationale for launching the phase 2 WSG-TP-II trial (NCT03272477) of neoadjuvant endocrine therapy plus trastuzumab (Herceptin) and pertuzumab (Perjeta) in patients with hormone receptor (HR)–positive, HER2-positive early breast cancer.

rationale for conducting the WSG-TP-II trial

 stemmed from the desire to explore treatment de-escalation strategies for patients with early-stage, hormone receptor-positive, HER2-positive breast cancer, Gluz begins. Traditionally, these patients receive standard neoadjuvant or adjuvant chemotherapy in combination with trastuzumab and pertuzumab for 18 to 24 weeks. However, given the potential adverse effects and burden of chemotherapy, the study, initiated in 2016, evaluated the possibility of safely reducing or eliminating one component of the standard treatment regimen, he reports. The trial compared 2 de-escalated treatment approaches to determine the safest regimen for patients with early-stage breast cancer without compromising efficacy, Gluz notes.

The WSG-TP-II trial was conducted in Germany and randomly assigned patients into 2 arms, he continues. One group (n = 100) received 12 weeks of neoadjuvant endocrine therapy combined with trastuzumab and pertuzumab, andthe second group (n = 107) received 12 weeks of paclitaxel alongside trastuzumab and pertuzumab. Following surgery, patients received 1 year of standard adjuvant endocrine therapy plus trastuzumab and paclitaxel with or without chemotherapy. The study protocol strongly recommended omitting adjuvant chemotherapy for those who achieved a pathological complete response (pCR) after 12 weeks of neoadjuvant treatment, he explains. Patients who did not achieve pCR in the neoadjuvant setting were recommended to receive adjuvant chemotherapy.

This trial demonstrated that 12 weeks of de-escalated neoadjuvant therapy with endocrine therapy or paclitaxel in combination with 1 year of trastuzumab plus pertuzumab is a safe regimen for chemotherapy de-escalation in this population.

Dr Gluz reports receiving honoraria for lectures and/or consulting and travel from Agendia, Amgen, AstraZeneca, Daiichi Sankyo, Eisai, Exact Sciences, Gilead, Lilly, MSD, Molecular Health, Novartis, Pierre Fabre, Pfizer, Roche, and Seagen.

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Oleg Gluz, MD, discusses the rationale for investigating neoadjuvant endocrine therapy plus trastuzumab and pertuzumab in HR+/HER2+ early breast cancer.

Oleg Gluz, MD, discusses data from the WSG-TP-II trial of neoadjuvant endocrine therapy plus trastuzumab and pertuzumab in HR+/HER2+ early breast cancer.ER2– breast cancer.

Dr Gluz on Survival Outcomes With De-Escalated Neoadjuvant Regimens in HR+/HER2+ Early Breast Cancercer

Oleg Gluz, MD, chief physician, Breast Center Niederrhein; West German Study Group, discusses survival data from the phase 2 WSG-TP-II trial (NCT03272477) of neoadjuvant endocrine therapy plus trastuzumab (Herceptin) and pertuzumab (Perjeta) in hormone receptor (HR)–positive, HER2-positive early breast cancer.

The WSG-TP II trial is the first prospective, multicenter, randomized study comparing the survival outcomes of two 12-week de-escalated regimens in patients with stages I through III HR-positive, HER2-positive breast cancer: neoadjuvant endocrine therapy plus trastuzumab and pertuzumab vs paclitaxel plus trastuzumab and pertuzumab. The trial's primary goal was to determine if patients could safely omit further adjuvant chemotherapy if they achieved a pathological complete response (pCR) following the 12-week neoadjuvant treatment.

 demonstrated the high efficacy and tolerability of the 12-week regimen, particularly when combining paclitaxel with trastuzumab and pertuzumab, Gluz reports. Notably, pCR rates were higher in patients receiving de-escalated chemotherapy vs those receiving the endocrine therapy regimen, he adds. Across all patients, approximately two-thirds achieved pCR after 12 weeks of treatment, emphasizing the efficacy of the chemotherapy-based approach, Gluz states.

However, long-term survival outcomes were comparable between both treated arms, Gluz continues. The 5-year event-free survival rates were 92.1% vs 94.8% with the endocrine- vs chemotherapy-based regimens, respectively. Respective overall survival (OS) rates for these arms were 100% vs 97.9%. These findings suggest that starting with a de-escalated treatment of endocrine therapy plus double HER2 blockade is safe, and chemotherapy can be reserved for patients who do not respond to the de-escalated regimen, he explains.

Overall, these results suggest that it is safe and feasible to begin treatment with 12 weeks of a fixed chemotherapy backbone plus double blockade in HR-positive, HER2-positive breast cancer, administering chemotherapy only to patient who do not achieve responses with the de-escalated approach, Gluz concludes.

Oleg Gluz, MD, discusses data from the WSG-TP-II trial of neoadjuvant endocrine therapy plus trastuzumab and pertuzumab in HR+/HER2+ early breast cancer.

Oleg Gluz, MD

Articles

Dr Gluz on the Rationale for the WSG-TP-II Trial in HR+/HER2+ Early Breast Cancer

Dr Gluz on Survival Outcomes With De-Escalated Neoadjuvant Regimens in HR+/HER2+ Early Breast Cancerer